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The top of the food chain can learn quite a bit from those at the bottom. While some fish and other lower organisms can regenerate tissue, we humans lag behind. Scientists at the MDI Biological Laboratory in Bar Harbor, Maine, are digging into the genes of these enviable organisms to learn how to activate such regenerative mechanisms in humans. They have just identified genetic regulators governing regeneration that are common across species.

Benjamin L. King, Ph.D. and Voot P. Yin, Ph.D., both with MDI, have identified these common genetic regulators in three regenerative species: the zebrafish, a common aquarium fish originally from India; the axolotl, a salamander native to the lakes of Mexico; and the bichir, a ray-finned fish from Africa.

Drs. King and Yin commented to OTW, “The long-term goal of our research at MDI Biological Laboratory is to understand how we may be able to enhance human regenerative capacity after injury. Humans can regenerate some tissues, such as blood, skin, liver and hair, but not others.

“There are other vertebrates, such as zebrafish, bichir and axolotl, which can regenerate many more different types of tissues, including limbs or appendages. At a cellular level, we knew that all three animals form a specialized tissue after wound healing, called the blastema. That is required for regeneration and is not formed in animals (like humans) that cannot regenerate appendages.

“The goal of this study was to determine whether these animals used the same genetic circuit to create and maintain the blastema tissue after injury. As these animals shared a last common ancestor more than 420 million years ago, it implies that nature has conserved these molecular mechanisms down through evolution. The identification of a common molecular pathway for regeneration raises the possibility that drugs could be developed to trigger the dormant molecular mechanism in humans.

“Given the remarkable regenerative capacity of limb tissues in all three model systems, we expected to identify some overlap in the molecular pathways during formation of the blastema, the critical first step in the regeneration process.

“But we didn’t expect to find that they were exactly the same, especially since we were looking at three different types of appendages: the axolotl limb, the bichir pectoral fin and the zebrafish tail. Again, our discovery implies that the molecular pathways for regeneration have been conserved during evolution.

“Orthopedic surgeons should know that the concept of limb and appendage regeneration in humans—although it may be years away—is within the realm of possibility.

“Also, they should know that this discovery could have important intermediate applications in two significant ways. Firstly, defining the molecular pathways governing regeneration could lead to the development of drugs that promote the regeneration of nerves at the site of an amputation in humans. This could, in turn, allow bioengineers to develop highly sophisticated prosthetic devices capable of interacting with these nerves. The demand for new medical strategies to address limb loss is increasing as a result of a dramatic rise in the number of amputations stemming from the increased worldwide incidence of diabetes.

“Secondly, enhancing the rate of tissue repair and regeneration could significantly hasten the rate of wound healing. If wounds, be they surgical or accident-induced, heal quickly, this will decrease the likelihood of infection and pain. Together, the immediate applications of limb regeneration research will result in significant improvements in patient quality of life.”